BEHAVIORAL ASSESSMENT OF NEURONAL PENTRAXIN 2 (NPTX2) AS A COGNITIVE RESILIENCE MECHANISM IN TRANSGENIC FISCHER 344 ALZHEIMER’S DISEASE (AD) RATS

Abstract

Alzheimer’s Disease (AD) is the most common form of dementia in aging populations and is characterized by circuit dysfunction and cognitive impairment[14]. Neuronal pentraxin 2 (NPTX2), also known as Narp, is an immediate early gene that is rapidly synthesized in hippocampal pyramidal neurons and regulates homeostatic scaling of synaptic activity in response to physiological stimuli. NPTX2 is downregulated in the brains of human AD patients, and protein levels correlate with cognitive performance and hippocampal volume[15]. This study aims to investigate the effects of a conditional knockout (cKO) of NPTX2 on rat hippocampal circuit function; in healthy Fischer 344 rats and novel transgenic Fischer 344 Alzheimer’s Disease (TgF344-AD) rats. Two cohorts of young rats (n=8) were tested on a behavioral battery assessing 1) hippocampus-dependent spatial learning and cued versions of the classical Morris water maze task, 2) locus coeruleus and hippocampus-dependent reversal learning versions of the Morris water maze, 3) medial prefrontal cortex and hippocampus-dependent temporal object task (TOT), and 4) midbrain-amygdala dependent elevated zero (EZ) maze task. Together, these behavioral data suggest a trend toward impaired spatial learning performance on the classical Morris water maze task, which may be attributed to an exacerbated effect of NPTX2 loss of function (LOF) with the pathological progression of amyloidosis and tauopathy in the TgF344-ADNPTX2 cKO rats compared to both the F344-NPTX2 cKO and wildtype F344 rats. Although the sample size is small, these results are promising for further behavioral and electrophysiological assessment of NPTX2 functionality in these rats.